Bulletin of the World Health Organization

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Mass treatment with ivermectin: an underutilized public health strategy

Rick Speare (1) & David Durrheim (1)

Ivermectin was a revolutionary drug
in the 1980s, the forerunner of a new
group of antiparasitic agents with activity
against both parasitic nematodes and
arthropods. Initially it was marketed for
veterinary use by Merck & Co. Inc.; it
was used largely for nematode control in
cattle, horses, pigs and dogs and became
the standard for control of the ectoparasitic
disease, scabies. The injectable cattle
formulation, Ivomec, became the world’s
most profitable veterinary drug (1).

Merck recognized Ivermectin’s
potential for human use, particularly in
the control of filariasis and most notably
onchocerciasis, the cause of river blindness
in West Africa, in the early 1980s.
In collaboration with WHO, nongovernmental
organizations and affected
national governments, the company
initiated a drug donation programme for
onchocerciasis control that subsequently
became the global model for philanthropic
partnerships between pharmaceutical
companies and countries unable
to afford the drug. Profits from the
veterinary use of ivermectin supported
this programme (1).

Merck’s patent on ivermectin
expired in 1996, though it was extended
for different periods in various countries.
Thus, other companies’ ivermectin
preparations are now commercially available.
Bioavailability of drugs depends
on formulation and manufacturing
processes, so the results obtained with
the ivermectin manufactured by Merck
may not apply to the new products. It
is thus encouraging to see clinical trials
evaluating new formulations of this valuable
drug.

Heukelbach et al. (pp.563–579)
report a study that investigates changes in
parasitological parameters and the occurrence
of side-effects after treatment with
ivermectin in a Brazilian community
heavily parasitized with intestinal helminths
and ectoparasites. The trial was
unblinded and uncontrolled, but provided
valuable information. Community
members, ineligible for ivermectin, were
treated with mebendazole, albendazole
or deltamethrin to achieve a high level of
coverage. Of particular importance was
the finding that ivermectin was highly
effective against Strongyloides stercoralis,
with a 94% reduction in prevalence that
was sustained for nine months. This
provided field evidence for a paper that
predicted that strongyloidiasis in heavily
endemic communities could be successfully
controlled with a highly effective
drug, owing to its low transmission
potential (2). The evidence presented by
Heukelbach et al. adds considerably to
evidence from smaller-scale controlled
trials (3–6).

Ivermectin has valuable public
health applications for controlling strongyloidiasis
and scabies (by breaking the
infection cycle through its therapeutic
effect) and filariasis, through its effect
on transmission. Ivermectin also acts
against other intestinal nematodes, but it
is not the most effective drug available.
In control programmes for filariasis,
ivermectin is the drug of choice in areas
with onchocerciasis, but can be replaced
by diethylcarbamazine for control of
other filarial diseases.

Since ivermectin’s use in the human
field, adverse reactions occurred in
50% or more of the population (7) and
ivermectin was “tainted” with a high
adverse reaction profile, despite evidence
that the majority of such reactions were
attributable to the interaction between
the drug and the disease, not to the drug
itself (8). A number of follow-up studies
have found that inadvertent filariasis
mass campaign use of ivermectin during
pregnancy has not been associated with
adverse pregnancy outcomes or negative
effects on pregnant women or their
offspring (9). The lack of serious adverse
events found in the study reported by
Heukelbach et al. is reassuring, as the
low incidence of minor adverse events
fell from 14% after the initial treatment
to 5% 10 days later.

It is time to capitalize on the full
public health potential of ivermectin.
Carefully designed studies to evaluate the
efficacy of community-wide ivermectinbased
control programmes for strongyloidiasis
and scabies in developing countries
are indicated, as are similar studies in
marginalized communities in developed
countries with high prevalences of these
two diseases, including indigenous
communities in Australia (10).

Ref. No. 04-015214

REFERENCES:

Collins K. Profitable gifts: a history of the Merck
Mectivan donation program and its implications
for international health. Perspectives in Biology
and Medicine 2004;47:100-9.